Bacterial meningitis is a significant cause of mortality and morbidity, especially in infants and young children. Although 85-95%of persons contracting meningitis currently survive, significantly neurological sequelae occur in approximately one third of these long-term survivors. The objective of the proposed research is to investigate the pathogenesis and prevent of Haemophilus influenzae meningitis. These studies will utilize an animal model. Our previous and continuing investigations have shown that intranasal inoculation of infant rats with Haemophilus influenzae type b results in bacteremia and meningitis. The histologic characteristics of the meningitis, the CSF findings and the age-related susceptibility of infant rats to sepsis and meningitis resemble the disease as it occurs in infants and children. Using this infant rat model, we aim to: 1) define host and microbiologic determinants of the pathogenesis (nasopharyngeal colonization, bacteremia and invasion of the blood-meningeal barrier) of H. influenzae b meningitis; 2) investigate the immunobiology of protection against H. influenzae mening tis induced by prior feeding of a non-pathogenic Escherichia coli; 075:K-100:H5, possessing capsular antigen (K-100) cross-reactive with the capsular polysaccharide of H. influenzae b.